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The Protective Effects of Riluzole on Manganese-Induced Disruption of Glutamate Transporters and Glutamine Synthetase in the Cultured Astrocytes

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Abstract

Chronic exposure to excessive manganese (Mn) can lead to manganism, a type of neurotoxicity accomplished with extracellular glutamate (Glu) accumulation. To investigate this accumulation, this study focused on the role of astrocyte glutamate transporters (GluTs) and glutamine synthetase (GS), which have roles in Glu transport and metabolism, respectively. And the possible protective effects of riluzole (a glutamatergic modulator) were studied in relation to Mn exposure. At first, the astrocytes were exposed to 0, 125, 250, and 500 μM MnCl2 for 24 h, and 100 μM riluzole was pretreated to astrocytes for 6 h before 500 μM MnCl2 exposure. Then, [3H]-glutamate uptake was measured by liquid scintillation counting; Na+-K+ ATPase and GS activities were determined by a colorimetric method; glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT-1), and GS mRNA expression were determined by RT-PCR and protein levels were measured by western blotting. The results showed that Mn inhibited Glu uptake, Na+-K+ ATPase and GS activities, GLAST, GLT-1, and GS mRNA, and protein in a concentration-dependent manner. And they were significantly higher for astrocytes pretreated with 100 μM riluzole than the group exposed to 500 μM MnCl2. The results suggested that Mn disrupted Glu transport and metabolism by inhibiting GluTs and GS. Riluzole activated protective effects on enhancing GluTs and GS to reverse Glu accumulation. In conclusion, Mn exposure results in the disruption of GLAST, GLT-1, and GS expression and function. Furthermore, riluzole attenuates this Mn toxicity.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (no. 30771834).

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Authors and Affiliations

  1. Department of Environmental Health, School of Public Health, China Medical University, Shenyang, People’s Republic of China

    Yu Deng, Zhaofa Xu, Bin Xu, Donghui Xu, Yawen Tian & Wanyu Feng

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  1. Yu Deng
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  2. Zhaofa Xu
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  3. Bin Xu
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  4. Donghui Xu
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  6. Wanyu Feng
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Correspondence to Zhaofa Xu.

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Deng, Y., Xu, Z., Xu, B. et al. The Protective Effects of Riluzole on Manganese-Induced Disruption of Glutamate Transporters and Glutamine Synthetase in the Cultured Astrocytes. Biol Trace Elem Res 148, 242–249 (2012). https://doi.org/10.1007/s12011-012-9365-1

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  • DOI: https://doi.org/10.1007/s12011-012-9365-1

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